Congestive heart failure (CHF) is the disease state wherein a weakened heart results in the inability to adequately pump blood throughout the body. CHF is a common cause of death in the hospital and is an expensive and time consuming condition to treat. Positive inotropic pharmaceuticals such as amrinone act by increasing the force of contraction of the heart without increasing heart rate and have been proposed to treat CHF. Presumably these agents produce their cardiotonic effects at least partly through inhibition of type IV phosphodiesterase.
Beta-blockers such as atenolol and propranolol may be given to persons who have suffered a heart attack in order to lessen oxygen consumption by the heart and prevent sudden death. However, if there is significant damage to the heart, there may be a lack of ability to pump forcefully and the negative inotropic effects of a beta-blocker may exacerbate an already dangerous situation.
Hydroxyalkylaminoalkyl substituted salicylamides having beta blocking or beta-stimulating activities are taught in European Patent 39,892 published Nov. 18, 1981. N-Heterocyclyl amines as beta agonists are taught in European Patent 236,624 published Sept. 16, 1987. European Patent 178,189 published Apr. 16, 1986 teaches pyridazinones having a phenyl group at the 6-position. Pyridazinones having an alkylaminophenyl group at the 6-position are taught in European Patent 259,835 published Mar. 16, 1988. 6-Phenyl-4,5-dihydro-3-(2H)-pyridazinones are further taught by W. V. Curran et. al. in J. Med. Chemistry, Vol. 17, No. 3 pp 273-281 (1974), by R. A. Slater in J. Med. Chemistry Vol. 31, No. 2, pp. 345-356 (1988), and in U.S. Pat. No. 4,397,854. Propanolamines having a heterocyclic moiety are taught in U.S. Pat. No. 4,608,383.